The Office of Cancer Genomics supports, leads, and/or manages six major research programs, listed in order of their inception Cancer Genome Anatomy Project (CGAP) The NCI CGAP is an online resource designed to characterize biological tissues and provide cDNA clones to the research community. To support these outcomes, CGAP provides a wide range of genomic data that include gene expression profiles of normal, precancerous, and cancerous cells (based on expressed sequence tags (EST) and serial analysis of gene expression (SAGE)), single nucleotide polymorphism (SNP) analysis of cancer-related genes, and the 50,000+-case Mitelman database of chromosomal aberrations in cancer. By collaborating with scientists worldwide, CGAP seeks to increase its scientific expertise and expand its databases for the benefit of all cancer researchers. Access to all CGAP data, clones, and analytic tools is made available to the research community through the CGAP web site and distribution system. Mammalian Gene Collection (MGC) The goal of the Mammalian Gene Collection (MGC), a trans-NIH initiative, is to provide full-length open reading frame (FL-ORF) clones for human, mouse, and rat genes. The MGC recently organized an international consortium of seven participants to create expression-ready clones for all Homo sapiens genes, which can be used by the research community for expression of proteins for large-scale proteomic analyses. In 2005, the project added the cow cDNAs generated by Genome Canada. Alternative methods based on gene-specific amplification have recently been developed to target the recovery of human and mouse genes absent from the MGC collection. Initiative for Chemical Genetics (ICG) Synthetic chemistry has enabled the creation of large collections of complex and diverse small molecules, patterned after natural products, which are tested for the ability to induce specific biological phenotypes. The NCIs Initiative for Chemical Genetics provides a systematic approach to study biology using such small molecules, to develop new screening tools and compounds, and to accelerate the development of new cancer strategies and therapies. As detailed below, the ICG focuses efforts on a number of deliverables, including biological assays, chemical libraries, a repository of chemical probes, and a scientific database. Discoveries made through the ICG program to date have resulted in more than 100 publications and 17 patents. The Cancer Genome Atlas (TCGA) The Cancer Genome Atlas (TCGA) pilot project is a three-year, $100 million-dollar collaborative effort between the NCI and the NHGRI that will test the feasibility of a large-scale systematic approach to identify genetic alterations in human cancer. The project, which was initially presented to the NCI BSA in November of 2005, was formally launched in FY 2006. The Atlas will profile three tumor types (brain, lung, and ovarian) by analyzing the expression profiles and genomic changes associated with each cancer sample. This characterization will be followed by the sequencing of genes and regions that are altered in a significant number of samples in each cancer type. The integration of these data types will provide insights into functional aspects of gene regulation and its role in cancer biology. In addition, the pilot project will create a comprehensive database, including clinical outcomes data, which will serve as a publicly-available resource to identify new genes and chromosomal regions of interest in cancer research. Advanced technology platforms will play key roles in the genomic analysis, and a caBIG-compatible infrastructure will facilitate data access by the scientific community. Although the pilot project is slated to run for three years, it is expected that results generated will be translated into findings with meaningful clinical impact well beyond this time frame. Cancer Genetic Markers of Susceptibility (CGEMS) CGEMS is a three-year, $14 million-dollar initiative to conduct whole-genome association studies to identify genes that confer susceptibility to prostate and breast cancer. Coordinated through the NCIs Division of Cancer Epidemiology and Genetics, the Core Genotyping Facility, and the OCG, the project capitalizes on new knowledge of single nucleotide polymorphisms (SNPs) in human genetic variation and technical advances in ultra-high-throughput genotyping. SNPs are the most common form of human genomic variation;most of the approximately ten million SNPs with a minor allele frequency greater than 5 percent occur in genomic segments in which they correlate highly with each other (i.e., they are in linkage disequilibrium). Data from the International HapMap Project Phase 2 indicate that a minimum of 550,000 carefully-chosen SNPs will be required to conduct a comprehensive whole-genome SNP scan. CGEMS is designed to conduct whole-genome scans in nested case-control studies of prostate and breast cancer from ongoing population-based cohort studies. Each whole-genome scan will analyze approximately 1,200 cases and 1,200 controls. Because the large number of SNP comparisons in a whole-genome scan will likely generate many false positive signals, follow-up sequential replication studies will be used to validate true positive associations. Using this procedure, CGEMS will assess the 15,000-20,000 top candidate SNPs from the whole-genome scans in follow-up case-control studies. Rapid public access to data generated by CGEMS will be facilitated by caBIG. The data generated by CGEMS prostate cancer study is available through the CGEMS data access portal. Therapeutically Applicable Research to Generate Effective Treatments (TARGET) The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative is committed to focusing genomics tools to rapidly identify potential therapeutic targets in childhood cancers so that new, more effective treatments can be developed in shorter time and ultimately bring new hope to children and their families who face the devastating burden of these diseases. The TARGET Initiative seeks to identify the genomic changes associated with Acute Lymphoblastic Leukemia (ALL) and Neuroblastoma, both childhood cancers. The research conducted by TARGET is divided into three distinct yet tightly integrated components that together form a system for selecting new molecular targets for the development of novel therapies for these childhood cancers: -Genomic Characterization: Gene expression studies (using high-resolution array-based methods to determine differences in the patterns of gene expression in cancer samples and non-cancerous samples) and genome structure studies (using high-resolution array-based methods to characterize genome structural changes that correlate with each cancer, such as chromosome region gains and losses) are integrated to provide a complete genomic "overview" of each cancer. -Gene Resequencing: Up-to-date genetic sequencing techniques are used to "read" genes that have been identified to have altered expression and/or structural alterations to identify the specific cancer-related mutations in the DNA sequence. -Identification of Therapeutic Targets: RNA interference (RNAi) is used to identify and initially validate potential targets identified from the genomic characterization and resequencing efforts.